A search for visionaries to crack human brain's code

WASHINGTON-- To crack the code of the human brain, Cori Bargmann figures it's best to keep an open mind.

As one of two leaders of a scientific "dream team" in the initial phase of President Barack Obama's ambitious $100 million project to map the brain, Bargmann said the first step is to find the right combination of people to set research priorities.

"You might start with people who are very senior and are household words in their fields, and then you may realize that what (you) actually need is the young Turk who's a visionary wild man," Bargmann said.

Bargmann, a neurobiologist at The Rockefeller University in New York, and William Newsome, a neurobiologist at Stanford Medical School in California, are the co-chairs of a committee announced by the White House on Tuesday for the Brain Research through Advancing Innovative Neurotechnologies Initiative. That long title has been dubbed BRAIN for short.

Both Newsome and Bargmann are at the top of the neurobiology pyramid, professors at premiere institutions, winners of dozens of scientific honors and awards, authors of research papers in prestigious journals. As Newsome noted wryly, "I don't need this aggravation, to some extent, but I think this is really important."

Bargmann, who recalls watching the first Apollo moon landing in 1969 as an 8-year-old, this year won a $3 million Breakthrough Prize in Life Sciences for her work on the genetics of neural circuits and behavior and synaptic guidepost molecules.

This project was something no scientist, so far, has turned down.

"If there's going to be a program to try to do something significant and the taxpayer's going to be involved in it, you make the time to try to help," she said. "As far as I know, everyone who was asked to help said yes."

The BRAIN effort isn't quite like any other, Bargmann said. Even the Human Genome Project had a more focused goal at the start: to determine the precise sequence of chemical "letters" that constitute the full complement of human DNA.

In contrast, before BRAIN tries to solve a single mystery of the human mind, it will build the scientific infrastructure to be able to ask the right questions. Like the U.S. space program in the 1960s, she said, BRAIN could get the public excited about science in a way that other research has not.

"I believe that brain science will be to the 21st century what quantum physics and DNA molecular biology were to the 20th century," Newsome said.

The ultimate goal is to decode brain activity to help researchers understand complex ailments ranging from traumatic brain injury to schizophrenia to Alzheimer's disease, which cost Americans $500 billion annually, according to Francis Collins, the head of the U.S. National Institutes of Health, who picked Newsome and Bargmann for the job.

The program would initially be funded with $100 million called for in the president's fiscal 2014 budget, set for release on Wednesday, which is subject to approval by Congress. That sum would be divided among the National Institutes of Health, the Defense Advanced Research Projects Agency (DARPA) and the National Science Foundation, with partners from the private sector.

Bargmann found it refreshing that Obama said the project would provide tools for understanding Alzheimer's and psychiatric disease, but he did not promise cures. "It isn't promising too much," she said.

She was also encouraged by support from two prominent Republicans: House of Representatives Majority Leader Eric Cantor of Virginia, and Newt Gingrich, former presidential candidate and former House speaker, who credited Obama for taking "a very important step toward the most dramatic breakthroughs in human health."

The Democratic president does not often get such enthusiasm from his Republican opponents.

Fast-developing technology makes this "a unique moment in time" to make this inquiry, Newsome said.

"I think the brain is the most mysterious and complex entity in the universe," he said by telephone. "And I think that new technologies that have developed within the last five years give us a shot at cracking open the problem of the brain in ways that previous generations of scientists never dreamed."

One of these technologies, Newsome said, is optogenetics, which uses genetic engineering to make certain nerve cells in the brain sensitive to different kinds of light, exciting or inhibiting these cells depending on the light's wavelength.

That means scientists can artificially switch the brain's circuits on or off during behavior to see how they contribute to essential functions like vision, learning and decision-making, Newsome said.

The other technological leap of the last decade has been the ability to record the electrical activity of hundreds or even thousands of neurons, a big improvement over the previous requirement of studying one neuron at a time. Since the human brain is composed of some 100 billion neurons - nerve cells that pulse with electrochemical signals - the one-at-a-time approach slowed research to a crawl.

It's not just the number of neurons, but seeing how these billions of neurons interact with each other that could make a map of the brain a reality.

That map is likely to be less like an atlas on paper and more like an online traffic video, Bargmann said, "because the brain is never the same in any two people, and it's not the same in one person at two different times."

Both Bargmann and Newsome are working in their own laboratories on pieces of this puzzle. Newsome focuses on the brain's way of mediating visual perception and visually guided behavior (see his lab's site at http://monkeybiz.stanford.edu ).

Bargmann's research aims to tackle a big subject - how environment and genes interact to shape human behavior - by looking at the relatively simple neurological system of a worm.